The objective of this research is to study genes in uninfected cells related to RNA tumor viruses. Endogenous virus-related genes may be involved in normal cell processes and in neoplastic disease. I plan to develop a marker rescue infectious DNA technique for avian leukosis-sarcoma virus genes, and to use this method to study endogenous virus-related genetic information in uninfected avian cells. Mutants of Rous sarcoma virus with lesions in genes for virus replication or for transformation will be used in marker rescue experiments to determine what viral genetic markers are represented in the DNA of uninfected chicken cells. The organization of endogenous virus-related genes will be studied by genetic linkage experiments and by mapping with restriction endonucleases. The possibility that changes in endogenous virus-related genetic information are associated with non-virus induced neoplastic disease will be investigated by using non-virus induced tumors as donors of DNA in marker rescue experiments. Inbred lines of chickens which differ in expression of endogenous virus-related gene products will be used as donors of DNA in order to study possible differences in their endogenous virus-related genes. The marker rescue infectious DNA technique will also be used to characterize endogenous virus-related genetic information in other avian species, such as pheasants, quail, turkeys, and ducks. In addition, endogenous murine leukemia virus DNAs in inbred lines of mice will be studied in transfection experiments.